This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adult stem cells from bone marrow have the potential to provide dramatic new therapies for neurological disorders. In addition to direct cell replacement by stem cells, current data provide evidence that neurotrophins and growth factors secreted by adult stem cells into the damaged CNS environment may provide a powerful stimulus for nervous system repair. Our work demonstrates that the primary effect of transplanted bone marrow stem cells is to stimulate the proliferation of endogenous CNS progenitors in the brain. We have proposed a series of experiments to test the central hypothesis that sub-populations of adult stem cells from human bone marrow can effectively engraft and repair the injured brain by influencing the proliferation and differentiation of endogenous CNS progenitors. The Specific Aims are: 1. To establish the molecular profiles of purified adult stem cell sub-populations from human bone marrow and compare them to CNS progenitor cells. 2. To determine the proliferation and differentiation patterns of endogenous CNS progenitors following the transplantation of different human stem cell sub-populations. 3. To evaluate the response of CNS progenitor cells following stem cell transplantation in an animal injured by stroke.